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壮观霉素的生物合成:在缺乏氨基糖苷类抗生素的宿主委内瑞拉链霉菌YJ003中异源生产壮观霉素和壮观胺。

Biosynthesis of spectinomycin: heterologous production of spectinomycin and spectinamine in an aminoglycoside-deficient host, Streptomyces venezuelae YJ003.

作者信息

Thapa L P, Oh T-J, Liou K, Sohng J K

机构信息

Department of Pharmaceutical Engineering, Institute of Biomolecule Reconstruction, Sun Moon University, Chungnam, Republic of Korea.

出版信息

J Appl Microbiol. 2008 Jul;105(1):300-8. doi: 10.1111/j.1365-2672.2008.03788.x. Epub 2008 Mar 18.

Abstract

AIMS

To obtain spectinomycin and spectinamine by heterologous expression into the biosynthetic deoxysugar (desosamine) gene-deleted host Streptomyces venezuelae YJ003.

METHODS AND RESULTS

The 17-kb spectinomycin biosynthetic gene cluster from Streptomyces spectabilis ATCC 27741 was heterologously expressed into Streptomyces venezuelae YJ003. Furthermore, the speA, speB and spcS2 encoded in the spectinomycin biosynthetic gene cluster of cosmid pSPC8 were also heterologously characterized to be responsible for the production of spectinamine.

CONCLUSIONS

The results of this study indicated that pSPC8 contains all the genes necessary for the biosynthesis of spectinomycin. We also concluded that SpeA, SpeB and SpcS2 are sufficient for the biosynthesis of spectinamine. We also verified that SpeB and SpcS2 show dual character in the biosynthetic pathway of spectinomycin in Streptomyces spectabilis.

SIGNIFICANCE AND IMPACT OF THE STUDY

This is the report regarding the expression of a biosynthetic gene cluster that gives rise to the production of aminoglycoside antibiotics in Streptomyces venezuelae YJ003. Therefore, this work may serve as a foundation for further research on spectinomycin biosynthesis and other aminoglycosides.

摘要

目的

通过在生物合成脱氧糖(去氧氨基糖)基因缺失的委内瑞拉链霉菌YJ003宿主中进行异源表达来获得壮观霉素和壮观胺。

方法与结果

来自壮观链霉菌ATCC 27741的17 kb壮观霉素生物合成基因簇在委内瑞拉链霉菌YJ003中进行了异源表达。此外,黏粒pSPC8的壮观霉素生物合成基因簇中编码的speA、speB和spcS2也被异源鉴定为负责壮观胺的产生。

结论

本研究结果表明pSPC8包含壮观霉素生物合成所需的所有基因。我们还得出结论,SpeA、SpeB和SpcS2足以进行壮观胺的生物合成。我们还验证了SpeB和SpcS2在壮观链霉菌壮观霉素生物合成途径中具有双重作用。

研究的意义和影响

这是关于在委内瑞拉链霉菌YJ003中表达导致氨基糖苷类抗生素产生的生物合成基因簇的报告。因此,这项工作可为壮观霉素生物合成及其他氨基糖苷类的进一步研究奠定基础。

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